Next Article in Journal
The Immobilization of an FGF2-Derived Peptide on Culture Plates Improves the Production and Therapeutic Potential of Extracellular Vesicles from Wharton’s Jelly Mesenchymal Stem Cells
Next Article in Special Issue
Administration of Spermidine and Eugenol Demonstrates Anti-Tumorigenic Efficacy on Metastatic SW620 and Primary Caco-2 Colorectal Cancer Spheroids
Previous Article in Journal
Small Molecules Inducing Autophagic Degradation of Expanded Polyglutamine Protein through Interaction with Both Mutant ATXN3 and LC3
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJMS
Volume 25
Issue 19
10.3390/ijms251910708
ijms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Drug Combination Studies of Isoquinolinone AM12 with Curcumin or Quercetin: A New Combination Strategy to Synergistically Inhibit 20S Proteasome

by
Carla Di Chio
†,
Santo Previti
†,
Josè Starvaggi
,
Fabiola De Luca
,
Maria Luisa Calabrò
,
Maria Zappalà
* and
Roberta Ettari
Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy
*
Author to whom correspondence should be addressed.
†
These authors equally contributed to this work.
Int. J. Mol. Sci. 2024, 25(19), 10708; https://doi.org/10.3390/ijms251910708
Submission received: 19 September 2024 / Revised: 1 October 2024 / Accepted: 2 October 2024 / Published: 4 October 2024
(This article belongs to the Special Issue Bioactive Natural Compounds: Protecting Plants and Promoting Human Health, 2nd Edition)
Browse Figures
Versions Notes

Abstract

In the eukaryotic cells, the ubiquitin–proteasome system (UPS) plays a crucial role in the intracellular protein turnover. It is involved in several cellular functions such as the control of the regular cell cycle progression, the immune surveillance, and the homeostasis. Within the 20S proteasome barrel-like structure, the catalytic subunits, β1, β2 and β5, are responsible for different proteolytic activities: caspase-like (C-L), trypsin-like (T-L) and chymotrypsin-like (ChT-L), respectively. The β5 subunit is particularly targeted for its role in antitumor activity: the synthesis of β5 subunit inhibitors could be a promising strategy for the treatment of solid and hematologic tumors. In the present work, we performed two combination studies of AM12, a recently developed synthetic proteasome inhibitor, with curcumin and quercetin, two nutraceuticals endowed of many pharmacological properties. We measured the combination index (CI), applying the Chou and Talalay method, comparing the two studies, from 50% to 90% of proteasome inhibition. In the case of the combination AM12 + curcumin, an increasing synergism was observed from 50% to 90% of proteasome inhibition, while in the case of the combination AM12 + quercetin an additive effect was observed only from 50% to 70% of β5 subunit inhibition. These results suggest that combining AM12 with curcumin is a more promising strategy than combining it with quercetin for potential therapeutic applications, especially in treating tumors.
Keywords: 20S proteasome; chymotrypsin-like activity; curcumin; quercetin; combination studies 20S proteasome; chymotrypsin-like activity; curcumin; quercetin; combination studies

Share and Cite

MDPI and ACS Style

Di Chio, C.; Previti, S.; Starvaggi, J.; De Luca, F.; Calabrò, M.L.; Zappalà, M.; Ettari, R. Drug Combination Studies of Isoquinolinone AM12 with Curcumin or Quercetin: A New Combination Strategy to Synergistically Inhibit 20S Proteasome. Int. J. Mol. Sci. 2024, 25, 10708. https://doi.org/10.3390/ijms251910708

AMA Style

Di Chio C, Previti S, Starvaggi J, De Luca F, Calabrò ML, Zappalà M, Ettari R. Drug Combination Studies of Isoquinolinone AM12 with Curcumin or Quercetin: A New Combination Strategy to Synergistically Inhibit 20S Proteasome. International Journal of Molecular Sciences. 2024; 25(19):10708. https://doi.org/10.3390/ijms251910708

Chicago/Turabian Style

Di Chio, Carla, Santo Previti, Josè Starvaggi, Fabiola De Luca, Maria Luisa Calabrò, Maria Zappalà, and Roberta Ettari. 2024. "Drug Combination Studies of Isoquinolinone AM12 with Curcumin or Quercetin: A New Combination Strategy to Synergistically Inhibit 20S Proteasome" International Journal of Molecular Sciences 25, no. 19: 10708. https://doi.org/10.3390/ijms251910708

APA Style

Di Chio, C., Previti, S., Starvaggi, J., De Luca, F., Calabrò, M. L., Zappalà, M., & Ettari, R. (2024). Drug Combination Studies of Isoquinolinone AM12 with Curcumin or Quercetin: A New Combination Strategy to Synergistically Inhibit 20S Proteasome. International Journal of Molecular Sciences, 25(19), 10708. https://doi.org/10.3390/ijms251910708

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop